From the Guidelines
Rasagiline and levodopa (combined with carbidopa) are crucial medications for managing Parkinson's disease, with rasagiline indicated for early disease as monotherapy and as adjunctive therapy in advanced disease, and levodopa being the gold standard treatment. The mechanism of action (MOA) of rasagiline involves preventing the breakdown of dopamine in the brain, thereby increasing dopamine levels and improving motor symptoms 1. On the other hand, levodopa directly addresses dopamine deficiency by crossing the blood-brain barrier and converting to dopamine, with carbidopa preventing peripheral conversion, reducing side effects, and increasing central availability 1.
Some key points to consider when prescribing these medications include:
- Rasagiline's common side effects, such as headache, joint pain, depression, and flu-like symptoms, and the potential for serotonin syndrome when combined with certain medications like antidepressants 1.
- Levodopa's common side effects, including nausea, orthostatic hypotension, and with long-term use, motor fluctuations and dyskinesias 1.
- The importance of taking levodopa-containing medications at least 30 minutes before meals to avoid interactions with dietary large neutral amino acids, and considering a protein-redistribution dietary regimen to maximize levodopa absorption and efficacy in patients experiencing motor fluctuations 1.
- The potential for levodopa to cause metabolic effects, including changes in lipid and carbohydrate metabolism, and the possible association with impaired nutritional status and risk for malnutrition 1.
In terms of specific guidance, levodopa should be started at low doses (e.g., 25/100 mg three times daily) and gradually increased based on symptom control, while rasagiline may be used earlier in the disease course, but levodopa provides more robust symptom control. It is essential to monitor patients closely for potential complications, including weight loss, micronutrient deficits, hunger, and dyskinesias, particularly when implementing a protein-redistribution dietary regimen 1.
Overall, the use of rasagiline and levodopa (combined with carbidopa) requires careful consideration of their mechanisms of action, potential side effects, and interactions with other medications and dietary factors to optimize treatment outcomes for patients with Parkinson's disease.
From the FDA Drug Label
Rasagiline tablets, a monoamine oxidase (MAO)-B inhibitor (MAOI), is indicated for the treatment of Parkinson’s disease Carbidopa and levodopa tablets are indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Rasagiline tablets are indicated for the treatment of Parkinson's disease (PD).
The indications for rasagiline and levodopa (carbidopa/levodopa) are for the treatment of Parkinson's disease. The mechanism of action (MOA) of rasagiline is as a monoamine oxidase (MAO)-B inhibitor (MAOI), while carbidopa works by decreasing peripheral decarboxylation of levodopa. The side effects of rasagiline include:
- Hypertension
- Serotonin syndrome
- Falling asleep during activities of daily living, daytime drowsiness, and somnolence
- Hypotension, especially orthostatic
- Dyskinesia
- Hallucinations and psychotic-like behavior
- Impulse control/compulsive behaviors
- Most common adverse reactions (incidence 3% or greater than placebo):
- Rasagiline monotherapy: flu syndrome, arthralgia, depression, dyspepsia
- Rasagiline used as adjunct without levodopa: peripheral edema, fall, arthralgia, cough, and insomnia
- Rasagiline used as adjunct to levodopa: dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall, and tenosynovitis 2 The side effects of carbidopa/levodopa are not explicitly listed in the provided drug labels, but it is mentioned that carbidopa may reduce nausea and vomiting 3
From the Research
Indications
- Rasagiline is indicated for the treatment of idiopathic Parkinson's disease as monotherapy or as adjunctive therapy to levodopa in patients with end-of-dose fluctuations 4
- Levodopa, in combination with a dopa decarboxylase inhibitor, is indicated for the treatment of Parkinson's disease (PD) 5
- Rasagiline is also indicated for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson's disease 4
Mechanism of Action (MOA)
- Rasagiline is a selective, irreversible, monoamine oxidase-B inhibitor 4
- Levodopa is a precursor to dopamine, and its combination with a dopa decarboxylase inhibitor increases the availability of dopamine in the brain, providing symptomatic benefit in Parkinson's disease 5
Side Effects
- Rasagiline is generally well tolerated, with the frequency and nature of treatment-emergent adverse events generally similar across clinical studies and between rasagiline and placebo groups 4
- Therapy with rasagiline appears to be associated with a low incidence of cognitive and behavioural adverse events 4
- The long-term use of levodopa is associated with the development of motor fluctuations and dyskinesias 5
- Rasagiline as adjunctive therapy to levodopa can reduce the total daily 'off' time and improve motor symptoms, with a similar incidence of dopaminergic adverse events as placebo 6